THE NATION: In Search of an AIDS Vaccine; Once More, H.I.V. Refuses To Play by the Rules

IN clinical science, researchers consider it axiomatic that a new drug or vaccine be shown to work in the lab before it is tried on people. If the product were proven ineffective, then, under ordinary circumstances, it would be abandoned. After all, the thinking goes, why waste years and millions of dollars testing something in humans when it fails in the laboratory?

But now the AIDS epidemic is causing researchers to rethink this seemingly straightforward procedure.

Recent laboratory tests fail to show that a single experimental AIDS vaccine actually immunizes against H.I.V. that is isolated from people. It is possible that the fault lies with the tests and not the vaccines. But even if scientists can't show that the laboratory tests are faulty, the National Institutes of Health is considering going ahead with human testing anyway. The need for a vaccine is so great, they argue, and the virus so poorly understood, that it might be worth the gamble.

The alternative would be to abandon vaccines that have cost millions of dollars and years to develop and start again from scratch. The question, said Dr. Peggy Johnston, acting deputy director of the Division of AIDS at the N.I.H., is "whether the need for a vaccine is greater than the risk."

With pressure coming from both AIDS advocacy groups and the pharmaceutical companies that have invested in the vaccines, Dr. Johnston said, it could be a difficult decision. Vaccine development has been going on for five years. Two years ago, the National Institute of Allergy and Infectious Diseases began preparing for human studies to see if the vaccines protect against H.I.V. These studies would involve over 5,000 people in the United States, last two to three years, and cost more than $10 million.

Normally it would be unthinkable to spend so much testing unproven vaccines. But some researchers argue that, so long as the vaccines are safe, even the most infinitesimal chance of victory is worth pursuing. And there is the human element. After so much waiting, it would be a real blow to go back to the drawing board. "Meanwhile," Dr. Johnston said, "an epidemic is raging." Perplexing Results

Until recently, researchers were optimistic about the dozen or so vaccines under development. Using components of H.I.V. grown in the laboratory, scientists hoped to design vaccines that would trick the immune system into generating protective antibodies. When they injected these vaccines into human volunteers, the volunteers indeed made antibodies. And those antibodies seemed to block H.I.V. grown in the laboratory.

But, said Dr. Dani Bolognesi, a vaccine researcher at Duke University, when tested against viruses isolated from people, the antibodies failed.

"That's where the surprise came in," he said. "I don't think I've ever seen anything quite like this."

Dr. David Ho, director of the Aaron Diamond AIDS Research Center in New York, suggested, however, that the researchers probably shouldn't have been so surprised. A few years ago, several biotechnology companies invested hundreds of millions of dollars in a study of what looked like an ingeniously designed new drug for people who already have AIDS. The drug, called soluble CD4, was a decoy. It was supposed to attract and latch onto the AIDS virus before it entered immune cells, blunting the invasion. The drug worked beautifully against viruses grown in laboratories, and so tests with humans began with great hopes and expectations. But the drug proved useless.

"We went back and asked why," Dr. Ho said. "We found to our surprise that viruses isolated from patients were 100- to 1,000-fold less sensitive" to the drug than viruses grown in the laboratory.

Part of the reason for the discrepancy, scientists believe, is that H.I.V. mutates so rapidly. But ultimately the source of the difference between wild and laboratory-grown H.I.V. is a mystery.

Dr. Ho said the biotechnology companies were incredulous. Now, he said, the drug makers have learned not to count on tests with laboratory-grown H.I.V. But, Dr. Ho said, the vaccine makers are reacting to the new vaccine data in the same way as the CD4 makers reacted to the data showing their drug did not work against naturally occurring H.I.V.: by blaming the test, or "assay," instead of their product. "In the recent discussions, people are saying, 'It's the assay, it's the assay,' " Dr. Ho said. He said these are reactions of people who are "not taking the problem seriously and trying to come up with excuses."

Dr. Ho said he thinks researchers will have to start over again, making vaccines from viruses isolated from patients. "It's not any harder," he said. "It's just that we have to start over."

Others disagree, saying that they cannot rule out problems with the assay without further study. Dr. Johnston said the N.I.H. is giving researchers until spring. But even if there is no obvious reason why the antibodies failed to block viruses isolated from patients, the pressure will be great to go ahead with human testing. Calls to Move Forward

Dr. Jack Obijeski, senior director for product development at Genentech, a biotechnology firm in South San Francisco, argues that, in the end, laboratory data can only tell you so much. The only true test of a vaccine is whether it protects people. "After all, the only data that's important for licensure and public health is clinical data," Dr. Obijeski said. "You can do these bloody assays until you have gray hair like myself and at the end of the day, it's still the clinical data." To delay, he said, hurts both companies that have invested years in vaccine development and vulnerable people, who need protection. "What are you going to do -- just sit there and waddle about?" Dr. Obijeski said. "We need to move forward."

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A version of this article appears in print on December 12, 1993, on Page 4004003 of the National edition with the headline: THE NATION: In Search of an AIDS Vaccine; Once More, H.I.V. Refuses To Play by the Rules. Order Reprints|Today's Paper|Subscribe